Neurodevelopment in Urban Environments: Role of Exposure to Ambient Air Pollution

描述（由申请人提供）：美国城市中越来越多的儿童暴露于城市环境中存在的各种神经毒素，这些毒素可能会损害他们发育中的大脑。在过去的十年中，环境健康科学家已经产生了关于暴露于道路交通排放（或交通空气污染[TAP]）的当今空气污染物（包括城市环境中的颗粒物和臭氧）的动物和人类神经毒性的令人信服的数据。实验动物模型已经证明，生命早期暴露于这些城市空气污染物会导致记忆障碍和长期的神经行为变化。与神经毒理学文献一致，来自横截面和纵向流行病学研究的先前数据显示，学龄或更小儿童中与TAP暴露相关的广泛的不良神经认知影响（包括低智商）。然而，目前尚不清楚TAP介导的不良神经认知效应是否持续到晚年，可能影响青少年和年轻人的学习成绩和教育程度。虽然毒理学家已经揭示了空气污染引起的前额叶和海马神经毒性的明确证据，但流行病学研究尚未研究更高的皮质控制功能（例如，执行功能[EFs];情绪调节）作为神经心理学介质的不利影响神经发育。以前的研究只提供了很少的洞察力的可能性，联合逆境导致暴露于神经毒性TAP和社会压力通常经历的城市居住的儿童。为了解决这些知识差距，该应用程序的主要目标是：（1）生成计划中的城市环境中神经发育长期研究所需的初步数据和基础设施;（2）开发一个概念框架，以阐明导致认知受损的神经心理学途径和暴露于城市空气污染物的长期社会经济后果。具体来说，我们提出了一个纵向研究的基础上正在进行的（2000年起）和良好的特点城市居住的南加州双胞胎队列（R 01 MH 058354）的全面数据的神经心理功能和结果评估从学龄（9-10岁）到年轻的成年人（19-23岁）。该应用程序利用正在进行的儿童健康研究的独特的、前瞻性收集的环境数据和资源，能够估计生命早期（1990年以后）暴露于空气污染的情况，并详细描述青少年期间城市内TAP暴露的情况。从两个理论模型（认知能力，压力反应和情绪失调）在心理健康研究中，我们将测试的假设，即EFs/情绪调节和他们的发展轨迹作为中心目标和神经心理学介质的后续不良影响的TAP暴露认知能力和社会经济成就。该项目的成功实施可能会极大地推进城市环境中发展神经科学的新兴领域。

DESCRIPTION (provided by applicant): The growing population of children in American cities is exposed to various neurotoxins present in urban environments which may damage their developing brains. Over the last decade, environmental health scientists have generated compelling data on neurotoxicity in animals and humans exposed to present-day air pollutants from road traffic emissions (or traffic air pollution [TAP]), including particulate matter and ozon in urban environments. Experimental animal models have demonstrated that early life exposures to these urban air pollutants result in memory impairment and long-term neurobehavioral changes. Consistent with neurotoxicological literature, previous data from both cross-sectional and longitudinal epidemiologic studies showed a wide range of adverse neurocognitive effects (including low IQ) associated with TAP exposure in school-aged or younger children. However, it remains unclear whether TAP-mediated adverse neurocognitive effects persist into later life possibly affecting academic performance and educational attainment in adolescents and young adults. Although toxicologists have revealed clear evidence of air pollution-induced neurotoxicity in the prefrontal lobe and hippocampus, epidemiologic studies have not yet examined higher cortical control functions (e.g., executive functions [EFs]; emotion regulation) as neuropsychological mediators of the adverse exposure-effects on neurodevelopment. Previous studies only provided very little insight on the likelihood of joint adversities resulting from exposures to both neurotoxic TAP and social stressors commonly experienced by urban-dwelling children. To address these knowledge gaps, the primary objectives of this application are to: (1) generate preliminary data and infrastructure needed for a planned long-term study on neurodevelopment in urban environments; and (2) develop a conceptual framework to elucidate neuropsychological pathways contributing to impaired cognition and long-term socioeconomic consequences of exposures to urban air pollutants. Specifically, we propose a longitudinal study built on an ongoing (2000- onwards) and well-characterized urban-dwelling Southern California Twin Cohort (R01MH058354) with comprehensive data on neuropsychological functions and outcomes assessed from school-age (aged 9-10) to young adults (aged 19-23). This application leverages the unique, prospectively-collected environmental data and resources of the ongoing Children's Health Study, enabling the estimation of early life (1990-onward) exposure to air pollution and detailed characterization of intra-urban TAP exposure during adolescents. Drawing from two theoretical models (cognitive vulnerability-stress response and emotional dysregulation) in mental health research, we will test the hypothesis that EFs/emotion regulation and their developmental trajectories serve as both the central target and neuropsychological mediators of subsequent adverse effects of TAP exposure on cognitive abilities and socioeconomic attainment. The successful performance of this project may greatly advance the emerging field of developmental neurosciences in urban environments.